The global crisis of multidrug resistance: how to face healthcare

Invited Commentary
Volume 5 Number 2 (June 2013) 99-101
The global crisis of multidrug resistance: how to face healthcare
associated infections without effective antibiotics?
Caterina Mammina
Department of Sciences for Health Promotion and Mother-Child Care “G. D’Alessandro”, University,
Palermo, Italy.
Received: April 2012, Accepted: May 2013.
Infections caused by multidrug resistant organisms
(MDROs) are severely challenging the healthcare
systems worldwide. Resistance to antibacterial drugs
is growing in both Gram positive and Gram negative
bacteria and is increasingly related to healthcare associated infections (HAIs). Undoubtedly, multiresistant Gram-negatives, especially carbapenem-resistant
Enterobacteriaceae (CRE) and Acinetobacterbaumannii, represent the cutting edge of crisis today (1).
Therapeutic options for these organisms are so extremely limited that old, previously forgotten drugs,
such as polymixins, have come back touse in absence
of robust data guiding dosage regimens or duration of
treatment. Moreover, panresistant strains have always
been reported (2).
Antibiotic resistance costs: the Alliance for the Prudent Use of Antibiotics (APUA) (http://www.tufts.
edu/med/apua/) has estimated for United States of
America alone a cost currently ranging between $24
billion and $38 billion a year. A report by the European Centre for Disease Control (ECDC) (http://www., focusing on four main types of
infection - bloodstream, lower respiratory tract, skin
and soft tissue and urinary tract infections -has highlighted that resistance is causing annually an economic burden of more than 900 million euros of extra
in-hospitalcosts and about 600 million days of lost
productivity. In this respect, poorer countries seem to
be even more disadvantaged. The poorer the country,
the larger is the proportion of its health-care budget
being absorbed by the cost of antibacterial drugs: indeed, antibacterial drug resistance forces healthcare
to turn from cheaper, but previously largely administered drugs, to more expensive alternatives (3).
Unfortunately, a synergistic combination of factors,
including the evolving healthcare delivery policies
and the shifting of patient demographics and underlying conditions towards higher risk profiles, is deeply
changing the landscape of HAIs. All countries are
involved in this global crisis with different weights
attributable to a variety of concurrent factors. Just to
name a few, poor healthcare resources, poor quality
of antibiotics, and sometimes over-the-counter availability of antibiotics, are likely playing an important
role in developing countries. In developed countries,
financial crisis and cutting resources to healthcare
systems along with the expanding population of old
and chronically ill patients, are worsening the situation. Finally, travels, transfer of patients and the socalled “medical tourism” are bridging the boundaries
between the developed and developing countries daily
(4). Worldwide reports show that MDRO’s infections
are increasingly serious and are in exorably spilling
over into the community, mainly through different alternative healthcare settings, such as long-term care
facilities (LTCFs) (5). Additionally, elderly and immunocompromised persons with comorbidities, who
are recurrently going back and forth between hospitals and LTCFs, contribute to the spread of MDROs
and likely represent the largest and misunderstood
reservoir of MDROs within the health care network
(2, 5).
The second driving force of the crisis is the falling number of new antibacterial drugs approved for
marketing: indeed, mainly in the field of the MDR
Gram negative bacilli, the pharmaceutical industry is
* Corresponding author: Caterina Mammina M.D.
Adress: Department of Sciences for Health Promotion and
Mother-Child Care “G. D’Alessandro”, University, Palermo,
Tel: +39-916-553623
Fax: +39-916-553641
E-mail: [email protected]
Mammina ET AL .
failing to deliver new antibacterials to replace those
made ineffective by resistance. Indeed, along several
decades,the pharmaceutical industry has funded and
pursued research and development on antimicrobial
drugs based on a return on investment in terms of future sales. However, in the last years, this business
model has become unsustainable: the costs of new
antibacterial development have increased under the
pressure of heavier regulatory burdens, but the chance
of success has parallelly declined by making investment in this field less and less attractive compared
to other types of longer-lived therapeutic agents, particularly those prescribed for chronic illness (2, 3).
So, the mainstay of any control measure for reducing MDRO’s infections is the implementation
of basic precautions based upon understanding of
how they are transmitted. A popular slogan is “back
to basics: hand hygiene!” (
safehealthcare/?p=1646)- very reasonable, but not so
easily applied. Transmission of MDROs is, indeed,
influenced by many different and intertwined issues,
including organizational and institutional factors.
Growing evidence is accumulating about the effects of
overcrowding, understaffing and bed occupancy rates
on the risk of MDRO’s infections. Indeed, several
studies have described over crowding and understaffing as factors promoting decreased healthcare worker
hand hygiene adherence and levels of cohorting, over
burdened isolation facilities and increased movement
of patients and staff between hospital wards (6, 7).
All these factors, which have been synthesized with
the term “organizational fatigue”, are associated with
higher nurse-patient interaction and cross-infections
rates (6, 7). So, the healthcare cost containment strategies aimed at obtaining greater efficiency by cutting the number of hospital beds, reducing the staff
and increasing patient throughput, are likely causing
negative side effects on patient safety and quality of
healthcare, putting at risk the efforts to control and
prevent MDRO’s infections. This stress on the healthcare systems may, indeed, actually increase hospital
costs due to rise in HAIs as a consequence of lapses in
infection control practices by over burdened healthcare workers, as previously observed in some reported outbreaks (6-8). Moreover, wide spread diffusion
of MDROs may result in ward closures and these, in
turn, in delayed elective admissions and over crowding of related wards and emergency units, triggering
vicious cycles where hygienic practices are unable to
prevent new infections.
IRAN. J. MICROBIOL. Vol. 5, No. 2 (June 2013), 99-101
Successful prevention or interruption of epidemic
MDROs have been achieved in both epidemic and
non epidemic settings, by implementing rigorous
measures at the local or, sometime, regional or national level (5). Evidence is sufficiently solid that
following implementation of strict control measures,
such as screening of new admissions in high-risk
wards and isolation/cohorting of colonized and infected patients, incidence of MDRO’s infections has
stabilized or declined (5). To find smart approaches is
imperative, but translating the huge quantity of white
and gray literature into practice needs knowledge of
local epidemiology which can be substantially different from place to place. According to the World
Health Organization (WHO), surveillance system deficiency amplifies antibacterial drug resistance (http://
International collaborative efforts would be required
to enable accurate and continuous monitoring of the
global spread of antibiotic-resistant bacteria. However, in developed countries, many studies have been
carried out, but through limited times and in single
facilities or small, poorly representative samples of
hospitals. Even worse, reliable data from vast areas
of Africa and Asia are scarce or absent. Effective surveillance systems aimed to obtain basic information
to customize prevention and control interventions
are essential and are not be considered an extra-cost.
Similarly, the role and skill of the microbiology laboratories in detecting and typing MDROs are critical
for infection prevention and control (5). Moreover,
proponents of changes to healthcare systems towards
a higher efficiency should learn to give more attention
to adverse events, such as spread of MDRO’s infections and consequent declining quality of care and associated costs.
Last, but not least, a more judicious policy of antibiotics use is urgently needed to be adopted on a
worldwide scale. Unfortunately, there are no easy and
universal answers to the question of how to prevent
excessive and inappropriate use of antibiotics. However, all opportunities are to be promoted to learn
from each other’s experience on how to control antibiotic use through restriction policies, educational
interventionsad dressing the issues of inappropriate
prescription and unnecessary self-medication, and
improving technologies to accurately and timely diagnose bacterial infections. Restriction of over-thecounter dispensing of antimicrobials without a prescription and regulation of the manufacture of drugs
to assure their purity and potency are also urgent in
all countries. Mean while, antibiotic over-use around
the world in livestock and fish farming is not to be
International efforts are also required to encourage
pharmaceutical companies to develop new antibiotics.
Recent closer attention to the problem of antimicrobial resistance from the WHO and many international
and national health agencies suggests that urgency of
the current situation is now better recognized. Some
global initiatives have also been launched. For instance, the British Society for Antimicrobial Chemotherapy (BSAC) has recently established “Antibiotic
Action” (, which is calling all interested parties – governments, healthcare
professionals, industry and charities – to identify and
implement solutions to “regenerate the discovery and
development of antibacterial drugs”.
The time for action is today according to the WHO,
to warrant cure for tomorrow.
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IRAN. J. MICROBIOL. Vol. 5, No. 2 (June 2013), 99-101